研究动态
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RFX 家族和相关基因的泛癌研究将 RFX8 确定为白血病的治疗靶点。

Pan-cancer investigation of RFX family and associated genes identifies RFX8 as a therapeutic target in leukemia.

发表日期:2024 Aug 15
作者: Zelong Cui, Yue Fu, Minran Zhou, Huimin Feng, Lu Zhang, Sai Ma, Chunyan Chen
来源: Experimental Hematology & Oncology

摘要:

多种转录因子和辅助因子由 RFX(调节因子 X)家族 (RFX1-8) 和相关基因(RFXAP 和 RFXANK)编码。越来越多的证据表明 RFX 家族和相关基因参与癌症的发生和进展。然而,之前没有研究关注这些基因的多组学分析,以评估它们在肿瘤进展中的作用。利用结合的 TCGA 和 GTEx 泛癌数据,我们研究了这十个基因的表达模式和生存概况。然后我们重点关注 RFX8 来分析其临床病理学和治疗特征。最后,我们对 RFX8 在急性髓系白血病 (AML) 中的功能进行了实验验证。RFX5 和 RFXANK 在大多数类型的癌症中表现出较高的表达水平,而 RFX6 在大多数类型的癌症中表现出较低的表达水平,其中 RFX8 在 LAML 中表达上调最多。 RFX2 和 RFXAP 在八种类型的癌症中显示出预后意义,RFX8 在六种类型的癌症中显示出显着的预后意义。这十个基因的表达在免疫亚型、肿瘤微环境和干性方面表现出特定的特征。 RFX8的表达与不同肿瘤分期、微卫星不稳定性(MSI)、肿瘤突变负荷(TMB)、免疫细胞浸润和免疫检查点表达相关。此外,还发现 RFX8 可以调节 AML 中的肿瘤发生和对白屈菜红碱的敏感性。我们的工作描绘了 RFX 家族和相关基因在泛癌背景下的概况以及 RFX8 在 AML 中的具体作用。这些发现可能为进一步研究癌症生物学中的这些基因提供线索。© 2024 作者。
Several transcription factors and co-factors are encoded by the RFX (Regulatory Factor X) family (RFX1-8) and associated genes (RFXAP and RFXANK). Increasing evidence suggests that the RFX family and associated genes are involved in the development and progression of cancer. However, no prior research has focused on a multi-omic analysis of these genes to evaluate their role in tumor progression.Using combined TCGA and GTEx pan-cancer data, we investigated the expression patterns and survival profiles of these ten genes. We then focused on RFX8 to analyze its clinicopathological and therapeutic features. Finally, we conducted experimental validation of RFX8 function in acute myeloid leukemia (AML).RFX5 and RFXANK showed higher expression levels, while RFX6 showed lower expression levels in most types of cancer, with RFX8 being the most upregulated in LAML. RFX2 and RFXAP demonstrated prognostic significance in eight types of cancer, and RFX8 showed significance in six types of cancer. The expression of these ten genes exhibited specific characteristics in immune subtypes, tumor microenvironment, and stemness. The expression of RFX8 was correlated with various tumor stages, microsatellite instability (MSI), tumor mutation burden (TMB), immune cell infiltration, and immune-checkpoint expression. Additionally, RFX8 was found to regulate tumorigenesis and sensitivity to chelerythrine in AML.Our work delineated the landscape of the RFX family and associated genes in the pan-cancer context and the specific role of RFX8 in AML. These findings might offer cues for further investigations of these genes in cancer biology.© 2024 The Author(s).